Sunday, September 14, 2008

Interview with Margery Silver and Thomas Perls

Summary: A group of researchers at Harvard Medical School have been trying to find out what it takes to reach the age of 100 or more.Assuming we're not all knocked off by the genes in our foods, then over the next few years there's going to be an explosion of one group in the population: those aged 100 or more.

A group of researchers at Harvard Medical School have been trying to find out what it takes to reach the age of 100. Is it more than having parents who lived a long time?

The results of the New England Centenarian Study suggest there is a lot more to it than genes. In fact, they've written a book called 'Living to 100: Lessons in Living to your Maximum Potential at Any Age'.

When I was in Boston a couple of weeks ago, I spoke to two of the principal investigators, Drs Margery Silver, a neuropsychologist and Dr Tom Perls, a physician with an interest in the elderly.

Tom Perls: We started of with what we call a population based study of centenarians in which we tried to find all the centenarians in a given geographic area. And we studied them, everything from their biological and medical state of affairs, to how they're doing functionally and what their cognitive status is like and so on. So we just basically tried to get a fair picture of what centenarians are like.

Norman Swan: So who have you got and where do they live?

Tom Perls: We go to these eight towns that are in close proximity of our Division on Ageing here at the Medical School, and basically it turns out that there were about 46 centenarians in this population of about 460,000 people, which comes out being one centenarian per 10,000 people in the population. That's about the going rate for most industrialised countries.

Norman Swan: Is that rate going up?

Tom Perls: It is going up, in fact centenarians are the fastest-growing segment of the population in the United States certainly, and then also probably in Europe. There are several good reasons for that: one is there was a dramatic decrease in childhood related mortality at the turn of the century, with the advent of vaccines and safe water supplies and better public health in general. So a lot of people, who could have gone on to be centenarians, died in their childhood. But now you see all these children living, and these children from the early part of the century are now going on to be today's centenarians.

Norman Swan: So these are really the first beneficiaries, the first real beneficiaries of the hygiene movement in the late 19th century?

Tom Perls: That's right. And the real boom is going to happen of course with people who were born in the 1920s when public health really took off. And of course, with the baby boomers next century when for instance around 2050 or so, we're going to see just a dramatic increase in the number of centenarians.

Norman Swan: Because whilst the problem largely, at least in non-indigenous populations, has been solved in terms of childhood mortality, what's happened since the war is that your life expectancy at say aged 50 has gone up dramatically, it's middle-aged life expectancy that's really gone up.

Tom Perls: That's absolutely right, and we're just seeing much better care of middle-aged and older people in terms of prevention, screening, as well as interventions in terms of major diseases like stroke and cardiovascular disease.

Norman Swan: OK, so you've got this study running of these centenarians. I thought it was more than that, I thought it was about 5,000, it's only 50.

Tom Perls: That's how the study began, with the 50 or so centenarians in this population-based study. But not too long after we started, we began to see that getting to very old age ran in families, and certainly everyone knows the adage 'old age runs in families' but there's been some evidence that maybe that wasn't true among gerontology circles. But here in fact, we were seeing that extreme old age anyway, does run in families. We got very interested in their pedigrees, or their family trees, and that has now - findings from that arm of our research has really thrust us in the direction of looking for genes that explain extreme old age, and now we're conducting an international study where we are looking for centenarians who also have brothers or sisters who achieved extreme old age. And actually looking for the genes that they have in common.

Norman Swan: You showed me a photograph just before we walked in here, of six generations. Just describe those six generations of this one woman's family.

Tom Perls: That was Sarah Knauss' family, who is currently thought to be the oldest woman in the world. Madame Calment died at the age of 122, and now her runner-up, so to speak, is Sarah, who lives out in Pennsylvania in the United States. This photograph that shows up at the end of this magazine, shows her sitting across sitting from her daughter, aged 95.

Norman Swan: Looking very spry, I might add.

Tom Perls: Yes, all of them looking terrific. Followed by her grandson, her great-granddaughter, her great-great-granddaughter, and her great-great-great-grandson.

Norman Swan: She's got all her marbles, she can remember things quite well?

Tom Perls: We actually did visit her with what's called the International Age Validation Committee.

Norman Swan: Proving that she was the oldest woman in the world?

Tom Perls: Well that's right. You know, when you come across somebody that rare, you really have to be very, very careful to make sure that she's the age that she is. And in fact that was done with Madame Calment. -

Norman Swan: Incidentally, Mme Calment is the lady in the South of France who we've actually had on the program, who could remember van Gough coming to her father's office, and the Eiffel Tower being built.

Tom Perls: Right. And despite remembering that, only passed away about a year ago. So we had to go through a similar methodology of proving Sarah's age, and so there was us from the New England Centenarian Study, a representative of the Danish Centenarian Study, a representative of the French Centenarian Study, and a demographer from the University of California, Berkeley, all looking very professorial, and deeming her worthy of the age that she says she is.

Norman Swan: Margery, what sort of questions do you ask of someone to find out what age they are?

Margery Silver: There was no birth certificate, because apparently at that time they did not record the birth. But there were marriage certificates and baptisimal certificates and enough other documents that fitted with the age she says she was, and fitted with the chronology in her family, that it was fairly certain proof.

Norman Swan: And did you test her? You're a neuropsychologist, did you test her?

Margery Silver: We asked her a few questions informally. We have not had permission from the family to test her. However, we are working on that, we would really like to test her, very much.

Norman Swan: Is she still living independently?

Margery Silver: No, she lives in a nursing home. Her 95-year-old daughter, who drove her automobile until about two months ago, just moved into an assisted living right across the street from her. She has fairly severe hearing impairment, but when you ask your questions, if she can hear you, her answers are very appropriate. She's sometimes very funny. At one point she was able to remember her age, part of the date, but not the exact date, and one of the examiners prompted her and she said, 'Oh, well, you know better than I do.'

Norman Swan: Your centenarians, you must have got to know them all pretty much personally.

Margery Silver: Yes, we have. I actually go into their homes to test them, to do the cognitive testing, and the personality testing. So usually I end up sitting at the kitchen table with the centenarian, usually several children, there to oversee things that help me in the testing, because they can often ask questions in a way that are more understandable if the centenarian is hard of hearing, for instance, or if English is a second language. And so it's kind of a family affair, round the kitchen table with grandchildren running in and out, and all kinds of things going on.

Norman Swan: Are they the same sort of person, the same sort of people? Do they have similar personalities? Before we get down to how well they're thinking and remembering, what about their personalities? Is there something about people who live to be 100?

Margery Silver: It's very interesting. The people we studied, the group we studied, is varied, as far as socioeconomic group, as far as ethnic background, but what we have found, our observations and in testing them, we now have some actual data that shows that there is a particular characteristic that is typical of centenarians. And that is that they are able to manage stress very well. And this doesn't mean that they've had stress-free lives. Sometimes you think these people live so long, they must have had really easy lives; some of them have had really very difficult, and even traumatic lives. There are holocaust survivors, there are women who were widowed at an early age and scrubbed floors to raise their children, and yet they seem to have the ability to roll with the punches.

Norman Swan: Flesh that out a bit more for me: they get stressed, how do they respond to it, compared to other people?

Margery Silver: They don't ignore it. For instance, they're very good at handling losses, and they seem to accept their losses, grieve them and then move on. And in many situations solve a problem, recognise it's hard, and then move on. They bounce back.

Norman Swan: They don't fester?

Margery Silver: They don't fester, that's a very good way of putting it.

Norman Swan: Does that mean that sometimes you might superficially think of them as cold, that they're not responding quite emotionally to things as you would expect?

Margery Silver: Oh no, not at all. They're not cold. As I say, they grieve and go on. One wonderful example of this, not from our study, is one of the surviving Delaney Sisters: these are the two sisters in New York -

Norman Swan: Who were the last children of slaves.

Margery Silver: Yes.

Norman Swan: And one just died a day or two ago.

Margery Silver: Yes. And the one who survived has written a book called 'Alone at 107' in which she talks about her grief and about her missing her sister, and it's all out there. And yet at the same time she's making plans to go out and do things, she has plans to write a new book, so she's moving on.

Norman Swan: These were two sisters who lived together most of their lives. One had been a dentist, and one died at the age of 95 leaving the other alone. Neither had married, neither had children.

Margery Silver: Right. Actually they were both over -

Tom Perls: Both lived to be over 100.

Margery Silver: Yes, one was I think 102 when she died. And the surviving one is 107.

Norman Swan: And she spoke about moving on?

Margery Silver: Yes. In fact her book that she wrote says 'Don't worry about me sister Bessie, I got plans'.

Norman Swan: What about their thinking ability?

Margery Silver: Well what we found, which is really optimistic, you know many people, including many scientists, believe that dementia is inevitable if you live long enough. There has been the idea that it increases exponentially in old age, and therefore if you get to be 100 everyone at 100 is going to be demented. And what we've found is that there is a sizeable group of 100-year-olds who are perfectly cognitively intact. And also because many of our subjects agree to donate their brains, we not only have seen that in the neuropsychological testing, but we've seen it in the neuropathological studies, and we've seen very clean, what our neuropathologist calls 'beautiful brains'. Actually we have a slide of the brain of one of our 100-year-old subjects, and the brain of a 52-year-old man with Alzheimer's Disease, and even an untrained eye can see that hers is a 'clean' brain, and that his is filled with the neurofibrillate tangles and plaques of Alzheimer's.

Norman Swan: When you add your groups of people to other people over 100 around the world who are being studied, what sort of percentage figure is it for people who remain intact, as you put it, intellectually?

Margery Silver: In the particular group that we studied in a 'slice of time' we found 21% who were completely cognitively intact, and other who were in a kind of questionable group. In other studies they found, some studies around 25% - 30%, I think one study even up to 40%. Now we're all using different ways of approaching it, and it's a question that needs a lot more research.

Norman Swan: And what percentage living independently?

Margery Silver: About 15% of our centenarians live alone. There's another large group that lives with family, and really would be considered independent in the sense that they do all the things, you know, they dress themselves, they feed themselves, they do all the things that are considered when you look at functioning, physical functioning.

Tom Perls: You know one very important point to make about how they're doing, is how they were doing, as well. Many people have to realise that these centenarians from our respective analysis of the data were completely independent doing things we would equate with 60, 70, 80 year olds, up through their early 90s. And it's only in the last five years or so of their lives where they experience illness. It's what we call a compression of morbidity, where they've lived the vast majority of their lives in excellent health, only to have a short period of time of their lives, at the end of their time, with poor health. And that really is one of the things we're so interested in, and why we study them, is this group either markedly delays, or entirely escapes diseases we normally associate with ageing.

Norman Swan: The key question for those people who would like to live to 100 is, is it simply writ in your genes? You can do a little bit by modifying your lifestyle, but the reality is, if you live to 100, you were actually born to live to 100.

Tom Perls: First of all, the very interesting point to make is a lot of people in the past may have said they'd never want to live to 100. And now what our centenarians are showing people is, my goodness, living to 100 is a wonderful thing to aspire to because look, they have another 30 or 40 years beyond what many people thought was the time to die, of opportunities and possibilities. And they did it because they lived such a long life in good health. They couldn't have gotten to their age in the first place, had they not done that.

Norman Swan: Is there a lower percentage of smokers, and people eating high fat diets? I mean if you were to ask them what they were doing in 1930, they were one of the few people not smoking around, is that the story?

Tom Perls: The story really does boil down to the genes actually. We think that having genes that allow you to both age slowly as well as escape or markedly delay diseases associated with ageing, like Alzheimer's, stroke and cancer, is extremely important to get to 100. A person would need what I would call genetic booster rockets to be able to get to 100. On the other hand, the good news is, people may say 'Well if it's all in the genes, what can I do about it?' but in fact I think that the very good news is that we believe that most people have the genes that will get them to their late 80s in excellent health. The reason that we don't see life expectancies like that on the average, is because people in general take such poor care of themselves. There's a lot of smoking, there's poor diets, the Aussies I know eat a tremendous amount of meat, they love their barbies, and these things, as we know from a lot of epidemiological data, increase mortality rates. If people realise that it was worthwhile to live to older age in good health because of the opportunities and possibilities that our centenarians show that can happen, I'm hoping that they'll spend more time taking better care of themselves exercising, eating appropriately.

Now the centenarians in general, they don't smoke, they never had a history of smoking, it's very rare that you'll find a centenarian with a history of obesity, and so there are some things that even centenarians, despite their wonderful genes, have to do I think, to get to their age. Now Mme Calment is an interesting example. This is the woman who lived to 122. She actually smoked some cigarettes up until the age of 116. Now to me that just says that she really had amazing genes to even to be able to counter the bad effects of smoking, and Lord knows if she didn't smoke she might still be alive today.

Margery Silver: I think there's another point to this centenarian personality, this stress-resistant personality. I do believe that the centenarians probably have a natural temperament that enables them to handle stress well. But we also know that we can all learn to handle stress well, and that one of the things they're telling us, or one of the things that we've learned from them is that it's really important to manage stress well in order to live a long time; that there's a real link with longevity.

Norman Swan: One of the features of getting old is that we blokes don't do it as well as the women. What's the gender split when you get to looking at 100-year-olds, is it all women?

Tom Perls: It isn't all women, but it is pretty dramatic. It's 85% women and 15% men. And so clearly women do get the upper hand on the men at these very old ages. And what's interesting is the men who do get to this very old age, they end up being better off than the women, functionally. And it really speaks for the fact that men who get into their 90s and into their 100s, have to really be in extremely good shape to continue to live at that age. Whereas women, they tend to be physiologically stronger, they can handle living with their diseases. If you give a man and a woman an equal amount of stroke or heart attack, the men will die of it and the women will live with it. So the woman lives with a double-edged sword, of yes, she can live longer but she must also live with diseases associated with ageing. On the other hand, the men, if they do live that long, they really have to be in spectacular shape.

Norman Swan: You, in a forthcoming book, have done some scientific palmistry, in other words questions that you could ask that might predict how long you're going to live. What sort of questions do you ask, is it possible to ask?

Tom Perls: Yes, in our book, 'Living to 100: Lessons in Living to your Maximum Potential at any Age', Margery and I have constructed a life expectancy calculator, and basically what that consists of is about 19 questions which both from our centenarian studies as well as work in public health, really we think make a tremendous difference whether or not a person has the ability to live to very old age. These would certainly be the ones many people would guess, things like whether you smoke or not, stress meat in your diet, or is it more fruit and vegetables. Actually there's some interesting ones that throw people off: for instance, we think flossing your teeth is very important, and we explain -

Norman Swan: Is this because of bugs and heart disease?

Tom Perls: Well that's exactly right. There's been a very strong link between chronic gum disease and the development of what we call immunal complexes that can lead to clogging up the blood vessels that feed the heart. And then there's some questions about your family, that's probably the only thing that you can't necessarily do something about in the questionnaire, which is whether you chose good parents and grandparents. But for the most part these are questions that people can really learn from in terms of modifying their lifestyles to live to an older age. You add up your score from your answers, and before your very eyes, your life expectancy appears before you, and we hope that the questions and the reasons for the questions, help people lead a longer life.

Norman Swan: So you can re-do yourself a year from now and it might have changed?

Tom Perls: That's right.

Norman Swan: I'm not sure I really want to know. Tom Perls, who by the way did part of his gerontology training in Melbourne, who along with Margery Silver runs the New England Centenarian Study at Harvard Medical School.

The book, just to repeat, is called 'Living to be 100: Lessons in Living to your Maximum Potential at any Age' by Tom Perls and Margery Silver. And it's published by Basic Books. It's not out in Australia yet, but you may be able to get it off the web.

And by the way, we've also found that women who have babies late in life live longer. That probably just reflects a young reproductive system.